Center for Neurobiology Stress, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Am J Gastroenterol. 2010 Apr;105(4):866-75. doi: 10.1038/ajg.2010.25. Epub 2010 Mar 2.
Alosetron is a potent, selective 5-HT(3) receptor antagonist prescribed for women with severe diarrhea-predominant irritable bowel syndrome (IBS-D) under a risk management plan (RMP). The RMP was implemented following cases of ischemic colitis (IC) and complications of constipation (CoC) associated with the use of alosetron. The objectives of this study were to characterize IC and CoC clinical features, outcomes, and incidence rates in the new restricted patient population to evaluate the effectiveness of the RMP in the prevention of serious outcomes.
Safety data from adverse event reporting from November 2002 through June 2008 were reviewed for probable and possible IC and CoC using the US Food and Drug Administration/sponsor-defined criteria and definitions. Evidence for IC included medical documentation, colonoscopy, and sigmoidoscopy+/-biopsy. Evidence for CoC included medical history and confirmation from health-care professionals.
Within the inclusion dates, 29,072 patients received 203,939 alosetron prescriptions. Although the absolute numbers of IC and CoC cases have declined, the incidence rates for IC and CoC (0.95 and 0.36 cases per 1,000 patient-years, respectively) were similar to rates during the postmarketing cycle before alosetron withdrawal. In patients with severe IBS-D receiving alosetron (n=998) or placebo (n=411) in clinical trials since reintroduction, incidence rates for IC were 4 and 2 cases per 1,000 patients, respectively. Rates for CoC were 2 and 0 cases per 1,000 patients in the alosetron and placebo groups, respectively. No mesenteric ischemia, surgeries, transfusions, or deaths occurred in patients with IC and no cases of CoC were associated with toxic megacolon, perforation, surgeries, transfusions, or deaths. IC and CoC cases were typically of short duration and all improved on prompt withdrawal of alosetron.
Serious outcomes associated with IC and CoC appear to be mitigated since introduction of alosetron under the RMP.
阿洛司琼是一种有效的、选择性的 5-HT(3)受体拮抗剂，根据风险管理计划（RMP），用于治疗严重腹泻型肠易激综合征（IBS-D）的女性。阿洛司琼的使用与缺血性结肠炎（IC）和便秘相关并发症（CoC）相关，因此实施了 RMP。本研究的目的是描述在新的受限患者人群中 IC 和 CoC 的临床特征、结局和发生率，以评估 RMP 在预防严重结局方面的有效性。
使用美国食品和药物管理局/赞助商定义的标准和定义，对 2002 年 11 月至 2008 年 6 月期间不良事件报告中的可能和可能的 IC 和 CoC 安全数据进行了审查。IC 的证据包括医疗记录、结肠镜检查和乙状结肠镜检查+/活检。CoC 的证据包括病史和医疗保健专业人员的确认。
在纳入日期内，有 29,072 名患者接受了 203,939 例阿洛司琼处方。尽管 IC 和 CoC 病例的绝对数量有所下降，但 IC 和 CoC 的发生率（分别为每 1,000 患者年 0.95 和 0.36 例）与阿洛司琼撤市后的上市后周期相似。在重新引入后的临床试验中，接受阿洛司琼（n=998）或安慰剂（n=411）治疗的严重 IBS-D 患者中，IC 的发生率分别为每 1,000 名患者 4 例和 2 例。阿洛司琼组和安慰剂组 CoC 的发生率分别为每 1,000 名患者 2 例和 0 例。IC 患者无肠系膜缺血、手术、输血或死亡，CoC 患者无一例与中毒性巨结肠、穿孔、手术、输血或死亡相关。IC 和 CoC 病例通常持续时间较短，所有病例在阿洛司琼迅速撤药后均得到改善。
自 RMP 引入以来，阿洛司琼的使用与 IC 和 CoC 相关的严重结局似乎有所缓解。
